Dichloromethane → 5-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide

HRID 1808552Notes

Reaction equation

HRID 1808552 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13](C(OC(C)(C)C)=O)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>CN(C=O)C.O>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[NH:13][N:12]=2)[CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:34])[CH3:35])(=[O:9])=[O:8])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 10340Sodium Carbonate2×HCID 580544941,1-Dimethylethyl 3-[[(5-chloro-2-thienyl)sulfonyl]({[2-(trimethylsilyl)ethyl]oxy}methyl)amino]-4-(methyloxy)-1H-indazole-1-carboxylate

Product 1

HCID 580544435-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamideYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1,1-dimethylethyl 3-[[(5-chloro-2-thienyl)sulfonyl]({[2-(trimethylsilyl)ethyl]oxy}methyl)amino]-4-(methyloxy)-1H-indazole-1-carboxylate (for a preparation see Intermediate 7) (3.12 g, 5.43 mmol) in DMF (20 mL) was added a solution of sodium carbonate (0.864 g, 8.15 mmol) in water (20 mL) at room temperature. A white suspension was obtained and a warming of the medium was noticed. The resulting suspension was stirred overnight at 80° C., the reaction mixture was then cooled to room temperature, and more sodium carbonate (300 mg) was added. The resulting mixture was then stirred at 85° C. After 3 h of stirring, 50 mL of water and 50 mL of DCM were added to the reaction mixture. The organic layer was partitioned and the aqueous layer was further extracted with 30 mL of DCM. The organic solutions were combined, dried with an hydrophobic frit and concentrated under reduced pressure. The crude oil was purified by chromatography on two 100 g Si cartridges on Flashmaster, eluting with a 0 to 25% gradient of EtOAc in cyclohexane, over 25 min. The pure fractions were combined to give the title product as an orange gum (1.62 g, 63%) LCMS (System A) RT=1.41 min, ES+ve m/z 474/476 (M+H)+. Impure fractions were combined and repurified by chromatography on a 70 g silica cartridge on Flashmaster, eluting with a 0 to 25% gradient of EtOAc in cyclohexane over 40 min. Fractions containing pure product were combined to give more of the desired product (277 mg, 11%)

Workup

  1. customA white suspension was obtained
  2. temperaturea warming of the medium
  3. temperaturethe reaction mixture was then cooled to room temperature
  4. stirringThe resulting mixture was then stirred at 85° C
  5. stirringAfter 3 h of stirring
  6. customThe organic layer was partitioned
  7. extractionthe aqueous layer was further extracted with 30 mL of DCM
  8. customdried with an hydrophobic frit
  9. concentrationconcentrated under reduced pressure
  10. customThe crude oil was purified by chromatography on two 100 g Si cartridges on Flashmaster
  11. washeluting with a 0 to 25% gradient of EtOAc in cyclohexane, over 25 min

Sources & evidence

ORD record
ord-f9951cb71a7843f2891f97f332e1ec9b
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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